Proteins Regulating Microvesicle Biogenesis and Multidrug Resistance in Cancer
1Discipline of Pharmacy, Graduate School of Health, The University of Technology Sydney, Sydney, Australia.
Abstract:
Microvesicles (MV) are emerging as important mediators of intercellular communication. While MVs are important signaling vectors for many physiological processes, they are also implicated in cancer pathology and progression. Cellular activation is perhaps the most widely reported initiator of MV biogenesis, however, the precise mechanism remains undefined. Uncovering the proteins involved in regulating MV biogenesis is of interest given their role in the dissemination of deleterious cancer traits. MVs shed from drug-resistant cancer cells transfer multidrug resistance (MDR) proteins to drug-sensitive cells and confer the MDR phenotype in a matter of hours. MDR is attributed to the overexpression of ABC transporters, primarily P-glycoprotein and MRP1. Their expression and functionality is dependent on a number of proteins. In particular, FERM domain proteins have been implicated in supporting the functionality of efflux transporters in drug-resistant cells and in recipient cells during intercellular transfer by vesicles. Herein, the most recent research on the proteins involved in MV biogenesis and in the dissemination of MV-mediated MDR are discussed. Attention is drawn to unanswered questions in the literature that may prove to be of benefit in ongoing efforts to improve clinical response to chemotherapy and circumventing MDR.
Insights
Microvesicles mediate intercellular communication and cancer progression. Research highlights proteins involved in microvesicle biogenesis and the spread of multidrug resistance (MDR) via these vesicles, offering insights into chemotherapy resistance.
Area of Science:
- Cell Biology
- Cancer Research
- Molecular Biology
Background:
- Microvesicles (MVs) are key in intercellular communication, influencing both normal physiology and cancer progression.
- The exact mechanisms initiating microvesicle biogenesis are not fully understood.
- Microvesicles from drug-resistant cancer cells can transfer multidrug resistance (MDR) traits to sensitive cells.
Purpose of the Study:
- To review recent research on proteins regulating microvesicle biogenesis.
- To discuss proteins involved in the intercellular transfer of multidrug resistance (MDR) via microvesicles.
- To identify knowledge gaps for improving chemotherapy response and overcoming MDR.
Main Methods:
- Literature review of recent studies on microvesicle biogenesis and MDR dissemination.
- Focus on the role of FERM domain proteins in efflux transporter function and MDR.
- Analysis of proteins implicated in the functionality of P-glycoprotein and MRP1.
Main Results:
- Microvesicles play a significant role in the spread of cancer traits, including multidrug resistance.
- FERM domain proteins are implicated in supporting efflux transporter functionality in both resistant and recipient cells.
- Intercellular transfer of MDR via MVs can occur rapidly, conferring resistance within hours.
Conclusions:
- Understanding MV biogenesis and MDR dissemination proteins is crucial for clinical applications.
- Further research into these proteins may lead to strategies to circumvent MDR.
- Addressing knowledge gaps can improve patient response to chemotherapy.
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